neoadjuvant immunotherapy plus crt versus neoadjuvant crt for locally advanced resectable escc

Conditions: Esophageal Squamous Cell Carcinoma Stage II; Esophageal Squamous Cell Carcinoma Stage III

Summary: the purpose of this study was to evaluate the safety, feasibility and outcome of anti-pd-1 antibody (tislelizumab, beigene) combined with neoadjuvant chemoradiotherapy versus neoadjuvant chemoradiotherapy followed by minimally invasive esophagectomy for locally advanced resectable esophageal squamous cell carcinoma (cii-iii stage) patient.

it is a prospective randomized phase ii\&iii clinical trial sponsored by shanghai zhongshan hospital with other twelve hospitals in china participating in. 476 patients with locally advanced resectable esophageal squamous cell carcinoma (cii-iii stage) are recruited and randomly assigned into the neoadjuvant chemoradiotherapy combined with immunotherapy group (ncrt plus anti-pd-1 group) and the neoadjuvant chemoradiotherapy group (ncrt group) according to the proportion of 1:1. the safety, efficacy of protocols and prognosis of patients are compared between the two regimens.

Eligibility criteria:
inclusion criteria: 1. histologically-confirmed esophageal squamous cell carcinoma and whose tissue samples were taken before treatment; 2. tumors of the esophagus are located in the thoracic cavity; 3. pre-treatment stage as clinical ii-iii (ajcc/uicc 8th edition) 4. age is between 18 years and 75 years; 5. eastern cooperative oncology group (ecog) performance status 0-1, and expected survival time ≥12 months; 6. adequate cardiac function. all patients should perform ecg, and those with a cardiac history or ecg abnormality should perform echocardiography with the left ventricular ejection fraction \> 50 %; 7. adequate respiratory function with fev1≥1.2l, fev1%≥50% and dlco≥50% shown in pulmonary function tests ; 8. adequate bone marrow function (white blood cells \>4x10\^9 /l; neutrophil \>2.0×10\^9 /l; hemoglobin \> 90 g/l; platelets\>100x10\^9 /l); 9. adequate liver function (total bilirubin \<1.5x upper level of normal (uln); aspartate transaminase(ast) and alanine transaminase (alt) \<1.5x uln); 10. adequate renal function (glomerular filtration rate (ccr) \>60 ml/min; serum creatinine (scr) ≤120 µmol/l); 11. the patient has provided written informed consent and is able to understand and comply with the study; exclusion criteria: exclusion criteria associated with cancer: 1. patients with histological non-squamous cell carcinoma; 2. patients with advanced non-operable or metastatic esophageal cancer; 3. pre-treatment stage as cm+, cn3 or ct4b(non-curatively-resectable verified by the local surgical investigator, ajcc/uicc 8th edition) or ctis-1a, ct1bn0; 4. patients with another previous or current malignant disease which is likely to interfere with treatment or the assessment of response in the judgement of the local surgical investigator; 5. patients who have received or are receiving other chemotherapy, radiotherapy or targeted therapy; other exclusion criteria: 6. patients with autoimmune diseases history; 7. recently or currently taking glucocorticoids or immunosuppressants; 8. patients who underwent immunotherapy in the past; 9. allergy to any antibody drugs or allergy to paclitaxel and carboplatin. 10. past or currently suffering from chronic or recurrent autoimmune diseases; 11. patients with active infection of immunodeficiency virus (hiv), hepatitis b virus (hbv) or hepatitis c virus (hcv); hiv seropositivity; hbv dna or hcv rna positive; 12. patients with organ transplantation (including autologous bone marrow transplantation and peripheral stem cell transplantation); 13. patients with severe systematic intercurrent disease, such as active infection or poorly controlled diabetes; coagulation disorders; hemorrhagic tendency or under treatment of thrombolysis or anticoagulant therapy; 14. any patient with a significant medical condition which is thought unlikely to tolerate the therapies. such as cardiac disease (e.g. symptomatic coronary artery disease or myocardial infarction within last 12 months), clinically-significant lung disease, clinically-significant bone marrow, liver, renal function disorder; 15. pregnant or lactating women and fertile women who will not be using contraception during the trial; 16. participation in another intervention clinical trial with interference to the chemotherapeutic or chemoradiotherapeutic intervention during this study or during the last 30 days prior to informed consent; 17. expected lack of compliance with the protocol.

Keywords: esophageal squamous cell carcinoma